Raimondi S C, Behm F G, Roberson P K, Pui C H, Rivera G K, Murphy S B, Williams D L
Department of Pathology and Laboratory Medicine, St Jude Children's Research Hospital, Memphis, TN 38101.
Blood. 1988 Nov;72(5):1560-6.
The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.
分析了57例儿童T细胞急性淋巴细胞白血病（ALL）的核型，以建立该疾病的细胞遗传学图谱。有三个问题特别令人关注。T细胞ALL中的染色体变化是否优先影响已定位编码抗原T细胞受体（TCR）基因的条带？涉及TCR基因区域的改变在B祖细胞ALL中出现的频率是否显著？该疾病中的染色体异常与T细胞个体发育阶段是否相关？相对较高比例的病例（65%）在初诊时具有假二倍体核型，大多数（58%）以易位为特征。易位的总体频率为44%，与我们实验室所有显带ALL病例中的频率相当。亚二倍体和超二倍体极为罕见（57例中仅4例）；16例（28%）具有明显正常的核型。在一半的易位病例（24例中的14例）中，断点位于已定位α和β链TCR基因的区域。在TCR基因座附近始终观察到的染色体断点为7q32 - q36（TCRβ链；n = 8）、14q11 - q13（TCRα链；n = 6）；其他常见断点为9p13 - pter（n = 8）和6q15 - qter（n = 9）。与335例B细胞前体ALL患者的对照组相比，T细胞病例中染色体改变在TCR基因座附近出现的频率显著更高（26%对1.5%，P = .0001）。23例患者表现为I期胸腺细胞发育（CD7 +、CD2 +、CD5 +、CD1 -、CD3 -、CD4 -、CD8 -），25例为II期（CD7 +、CD2 +、CD5 +、CD1 +、CD3 -、CD4 + / -、CD8 + / -），9例为III期（CD9 +、CD2 +、CD1 -、CD5 +、CD3 +，以及CD4 +或CD8 +）。细胞遗传学结果与T细胞个体发育之间唯一具有统计学意义的关联是，I期胸腺细胞病例中正常核型的频率较高，II期病例中假二倍体的频率较高。特定易位与胸腺细胞成熟水平之间没有明显关系。我们的研究结果表明，大多数T细胞ALL儿童具有假二倍体核型，尽管令人惊讶的是，有很高比例的儿童缺乏可证实的异常克隆。特定的染色体变化似乎与本研究中定义的T细胞个体发育的离散阶段无关，但它们优先发生在含有TCR基因的条带中。
